Protective role of NHE-3 inhibition in rat renal transplantation undergoing acute rejection.

Abstract

Acute rejection in renal transplantation disturbs solute and volume maintenance in humans accompanied by delayed graft function and poor prognosis. We recently reported that decreased expression and function of Na+/H+ exchanger type 3 (NHE-3) in proximal tubules and epithelial Na+ channels and aquaporin 2 in collecting ducts are major mechanisms involved in Na+ and water imbalances shortly after transplantation in rat undergoing acute rejection. We performed kidney transplantations in rats with bilaterally nephrectomized recipients with acute rejection and, in addition, systemically administered a specific inhibitor of NHE-3 (NHE-I). NHE inhibition in acute renal failure was shown to improve tubular function and recovery. The aim of this therapy was to reduce energy consumption of the graft and preserve NHE-3 function. Imbalances in electrolyte excretion declined in NHE-I-treated animals and NHE-3 activity was preserved. Observed NHE-I-dependent changes in electrolyte excretion, polyuria, and reduced protein reabsorption in the acute postoperative phase are predictors of favorable graft outcome in humans.

• Authors: Stefan Reuter, Ana Velic, Bayram Edemir, Rita Schröter, Hermann Pavenstädt, Gert Gabriëls, Markus Bleich, Eberhard Schlatter
• Journal: Pflugers Archiv : European journal of physiology (Pflugers Arch) Vol. 456 Issue 6 Pg. 1075-84 (Sep 2008) ISSN: 0031-6768 [Print] Germany
• PMID: 18335234 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• SLC9A3 protein, human
• Slc9a3 protein, rat
• Sodium Channels
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers
• Adenosine Triphosphate
• Sodium

Topics

• Acute Disease
• Adenosine Triphosphate (metabolism)
• Animals
• Blotting, Western
• Down-Regulation (drug effects)
• Graft Rejection (pathology, prevention & control)
• Hydrogen-Ion Concentration
• Immunohistochemistry
• Immunosuppression Therapy
• Kidney Transplantation (physiology)
• Kidney Tubules, Proximal (drug effects, metabolism, pathology)
• Male
• Nephrectomy
• Rats
• Rats, Inbred Lew
• Reverse Transcriptase Polymerase Chain Reaction
• Sodium (metabolism)
• Sodium Channels (metabolism)
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)